Dokument: Neue kindgerechte Arzneiformen für den Wirkstoff Natriumbenzoat
| Titel: | Neue kindgerechte Arzneiformen für den Wirkstoff Natriumbenzoat | |||||||
| Weiterer Titel: | Novel paediatric formulations for the drug sodium benzoate | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=8262 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20080710-102728-5 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Krause, Julia [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Dr. Breitkreutz, Jörg [Gutachter] Prof. Dr. Kleinebudde, Peter [Gutachter] | |||||||
| Stichwörter: | Pharmazeutische Technologie, Lipidpellets | |||||||
| Dewey Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit | |||||||
| Beschreibungen: | In der Arbeit wurden neue Arzneiformen, eine Infusionslösung und geschmacksmaskierte Pellets, mit Natriumbenzoat als Arzneistoff entwickelt.
Die Infusionslösung ist für die Notfallversorgung von Neugeborenen mit non-ketotischer Hyperglycinämie oder Harnstoffzyklusdefekten bestimmt. Im Gegensatz zu den bisher in Krankenhausapotheken hergestellten Infusionslösungen bietet die neu entwickelte Infusionslösung den Vorteil, das Risiko von Hypernatriämien zu verringern. Die geschmacksmaskierten Pellets sind für Kleinkinder und ältere Patienten gedacht, die in der Lage sind, diese kleinen Partikel zusammen mit der Nahrung einzunehmen. Im Gegensatz zu den bisher existierenden Natriumbenzoat-Granulaten kann bei den neu entwickelten Pellets auf eine Geschmacksmaskierung, die auf einem separaten Prozess beruht, verzichtet werden. Dies wurde durch verschiedene in-vivo und in-vitro Untersuchungsmethoden gezeigt. Der Mechanismus der Geschmacksmaskierung, welcher erstmals in dieser Arbeit entdeckt und beschrieben wurde, beruht auf einer in-situ Bildung von Lipidschichten.Novel drug formulations with sodium benzoate as an active ingredient were developed in the present work: an infusion solution and taste masked pellets with lipid binders. The infusion is intended for the use in neonates with non-ketotic hyperglycinemia or urea cycle defects and for emergency cases. In contrast to common infusions prepared in hospital pharmacies it lowers the risk of hypernatremia in newborns. The solution underwent stability testing for 2 years meanwhile the testing of different stopper material as vial closures was included. The formulation was stable during the tested time period, since the content of the tested ingredient was in between 95% and 105% of the nominal content for all batches. Only one stopper variety, the bromobutyl rubber stoppers, were evaluated as insufficient, as the pH value changed significantly over the tested period. The taste masked pellets are intended for infants and elder patients who are able to swallow small-sized particles together with food. In contrast to already existing pellets with sodium benzoate the newly developed pellets do not need a polymer coating for an efficient taste masking of the bitter and salty tasting sodium benzoate, as demonstrated by different in vitro and in vivo taste assessment methods. The pellets show a self-coating mechanism which was discovered and described in the present work for the first time. It is based on the production process through which an approximately 10 µm layer of lipids is formed around the pellet surface which acts as a diffusion barrier and masks the unpleasant bitter and salty taste. This mechanism is based on a temperature dependent drug release. Selection of appropriate lipid formulations influence the diffusion through this layer and release profiles can therefore be fitted to desired kinetics The taste assessment was also performed in vitro using novel chemometric sensor systems called “electronic tongues”. Two of these e-tongues were used for the determination of taste of 5 different pellet formulations all containing sodium benzoate. The two e-tongues were evaluated and compared in their handling and measurement routine, data analysis and ability for the prediction of taste. Correlations between taste values from the human taste panel as well as concentration of released sodium benzoate and data from the e-tongues were possible. E-tongues offer valuable alternatives to the common method of human taste panel tests for the evaluation of taste, especially in critical cases such as formulations for the paediatric populations, where taste assessment studies are difficult to conduct, amongst others due to regulatory and developmental issues. | |||||||
| Rechtliche Vermerke: | Aus patentrechtlichen Gründen bis 31.01.2009 gesperrt! | |||||||
| Lizenz: |  Urheberrechtsschutz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät » WE Pharmazie » Pharmazeutische Technologie und Biopharmazie | |||||||
| Dokument erstellt am: | 02.02.2009 | |||||||
| Dateien geändert am: | 15.07.2008 | |||||||
| Promotionsantrag am: | 13.05.2008 | |||||||
| Datum der Promotion: | 13.06.2008 |
